For the sake of drug discovery, as a method for screening an effective drug, a technique (cell based assay) has been widely employed which determines whether or not a living cell is susceptible to a drug. In the related art, when an effect of the drug is conveniently evaluated, a method has been used which determines whether or not a target molecule physically binds to a target drug. In contrast, a physiological response of a cell serving as a target of the drug is directly measured, thereby enabling the effect of the drug to be more accurately evaluated.
This cell based assay technique is used not only for the drug discovery but also in various fields. For example, as an allergy test, it is possible to determine whether a patient responds to a specific allergen or to determine a possibility that a certain substance causes an allergic reaction. In addition, when a medicine such as an anticancer drug is administered, this technique is also applicable to personalized medicines for selecting and administering the most effective drug.
A typical procedure for the cell based assay technique is as follows. First, cells serving as a measurement sample are cultured or collected from a subject. Next, the cells are fixed to a surface of a substrate such as a sensor chip. Then, a reaction reagent is added and brought into contact with the measurement sample. The cells are observed and measured using means such as a fluorescence microscope. In this manner, the obtained data is analyzed so as to determine whether or not there is a change in the cells or how big the cells are. As a method of observing and measuring the response from the cells, a method of using surface plasmon resonance (SPR) has been recently used in the above-described biology, in addition to a general fluorescence observation method.
PTL 1 discloses a technique in which an SPR imaging method applying SPR is used as the cell based assay method so as to observe and measure the response from the cells. Laser light incident on a glass substrate is incident on an interface F between the glass substrate and a thin metal film at an incidence angle θ=56° which satisfies the total reflection condition and generates a phenomenon of the surface plasmon resonance. The laser light reflected on the interface F is emitted from the glass substrate and a prism, and is incident on an objective lens. The objective lens magnifies an object image at a predetermined magnification, and forms an image on an image plane. The laser light emitted from the objective lens reaches the image plane of an imaging unit. For example, the imaging unit is a charge coupled device (CCD) image sensor or a complementary metal oxide semiconductor (CMOS) image sensor. An intensity image corresponding to the two-dimensional intensity distribution of reflected light of a parallel beam incident on the interface F of the prism, that is, a reflection intensity image is formed on an image plane of the imaging unit. Living cells C1 and C2 which are measurement targets of the active reaction are attached onto a surface (one surface) on a side opposite to the interface F in the thin metal film. A flow cell serving as a channel through which a liquid flows is disposed on the thin metal film. The flow cell is a channel through which the liquid to be exposed to living cells C1 and C2 set on the thin metal film flows. The flow cell is connected to a liquid supply unit. The liquid to be exposed to the living cells C1 and C2 is supplied into the flow cell from the liquid supply unit. FIGS. 4(A) to 4(C) in PTL 1 illustrate changes in images of the reflection intensity images after 0 minutes, 10 minutes, and 20 minutes from when the living cells C1 and C2 are not stimulated. FIGS. 5(A) to 5(C) in PTL 1 illustrate changes in images of the reflection intensity images after 0 minutes, 10 minutes, and 20 minutes from when the living cells C1 and C2 are stimulated. As is apparent from the comparison between FIGS. 4 (A) to 4(C) and FIGS. 5(A) to 5(C), it is understood that if the living cells C1 and C2 react to an external stimulus, luminance of a portion corresponding to the living cells C1 and C2 is changed.
In addition, PTL 1 also discloses a technique for improving the throughput by concurrently analyzing a plurality of cells in a multi-well chamber and a plurality of stimuli in an imaging field of view of SPR. A basophilic solution is injected into the multi-well chamber (for example, those which have empty wells formed in a matrix shape so that an injected solution is isolated) as illustrated in FIG. 11(A) in PTL 1, by using a liquid droplet ejecting device as described when the external stimulus is ejected or by means of pipetting. Furthermore, an allergen administrating multi-chamber designed to match the multi-well chamber into which the basophilic solution is injected is also prepared. This allergen administrating multi-chamber is configured similarly to the above-described liquid droplet ejecting device. Different allergens are preferably concurrently administered to each well into which blood is injected. Therefore, the disclosed technique utilizes a cell activity analyzing device and a cell activity analysis method according to the present embodiment.